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Topic: What do you do when you can't tolerate antidepressants? (Read 1561 times)

I have suffered with panic disorder for roughly 14 years now, along with occasional episodes of generalised anxiety disorder and depression thrown in for good measure (the depression comes mostly after prolonged periods of anxiety, though, so it is more of a secondary problem). Prior to that, I was always a "worrier" as a child, so I guess I've probably always had a problem.

Up until the last year or so, my panic disorder was relatively controlled. I could get by so long as I avoided certain things (not good, I know, but it worked), and carried around benzos for use as needed, but now I have developed fully-fledged agoraphobia.

Last year was really bad. I got stuck in the house for a few weeks, and it took me a long time to be able to go out and do things again (like work or shopping), but I haven't improved much. I'm still stuck within roughly a 5 km radius of my house, and even within that radius there are places and situations that I can't be in for fear of getting stuck. (e.g., driving on certain roads, meetings at work, buying too many things at the supermarket).

I think I was able to manage up until now, because I could accept that the panic attacks weren't dangerous, just unpleasant. Well, since then, I've been diagnosed with a heart condition (SVT), and the panic attacks can (and have) triggered episodes of SVT. So now I'm desperate to avoid anything that could trigger a panic attack, because SVT is really not nice and pretty incapacitating when it happens. I have atrial tachycardia, too, so there's not really anything I can do to stop the episodes. I just have to wait it out.

The thing is, I just don't know what to do anymore. There's never ever been a period in my life where I've been totally free of anxiety, so I think I am one of those people who will probably always have to take some kind of medication. I'm ok with that, but I can't tolerate the medications that are usually prescribed for this sort of thing.

Antidepressants don't work and/or have intolerable side effects. Most make me hypomanic, within as little as a few days. The only one I could tolerate was mirtazapine (30 mg), and that was only if I also took quetiapine (an antipsychotic) at the same time. I was on that combination for 5 months or so, but it was horrible, so I came off both.

I have tried at least one antidepressant from the following classes: SSRI, SNRI, TCA, and NaSSA, so no one can say I haven't given them a good go. They are all way too activating for me, even at tiny doses. The only difference between them is the side effects. (This was all under the supervision of a psychiatrist by the way, so I've been doing the right thing, but I don't think even he knows what to do in my case).

I have also tried CBT. I really stuck with it (did it for well over a year), but it was like trying to put out a forest fire with a water pistol. Pretty much a waste of time.

Right now, I'm getting by (barely) with benzos. My GP (who I am too agoraphobic to actually go and see in person) has been prescribing me diazepam (10 mg per day in divided doses). I've been taking them for 3 or 4 months now, but it's not enough, and she doesn't want to give me a higher dose. I understand the issues of dependence and possible tolerance, but I think benzos may be my only hope. Over the years, I have used temazepam (prn), alprazolam (prn), oxazepam, and diazepam, and they've helped (with minimal side-effects). The cognitive side effects of diazepam are a bit of a pain (my short-term memory is pretty much gone, but I can live with that if it means no more anxiety).

I have also been experimenting with metoprolol (a cardio-selective beta blocker), which my cardiologist gave me for the heart problem. It does help with the anxiety, but I'm super sensitive to meds that lower my blood pressure and I don't think I can get it up to a therapeutic dose to block panic attacks. The most I have taken is 25 mg, which will drop my blood pressure down to around 95/70 and lower my resting heart rate to around 50. That's no big deal, but given that 25 mg has proved utterly useless at blocking the effects of a panic attack (my heart rate went right up to 160-180 during one), I am worried about going to a higher dose, since the effects on my blood pressure (and maybe heart rate) will probably be more pronounced.

So... I'm wondering, what can I do? Antidepressants are not an option. I am never going to take another antipsychotic again, and I'm not too keen on the idea of mood stablisers or anticonvulsants (assuming that the last two even work for panic at all -- the evidence seems pretty sketchy).

My GP has referred me back to my psychiatrist, but I'm not sure that he is going to know what to do either. Best case scenario is he tells my GP it's ok to prescribe a higher dose of benzos.

Does anyone here have any experience of being in a situation like this (i.e., where you can't take antidepressants), and/or does anyone have any experience of long-term benzo use?

Just how likely is tolerance? From what I've read in the scientific literature, some people become tolerant quickly, while others never seem to develop it. (Dependence is another matter, but I don't give a damn about that).

I could really use some advice, because I've just about reached the limit of what I can cope with. Although I'm in no immediate danger of ending my life, life does seem pretty pointless. Anxiety has ruined everything: my social life, my career, and I sometimes I really do wonder if I'd be better off dead. Agoraphobia makes me feel like I'm in prison, and it's all just so draining.

U and I are similar. Except mine didn't go into agoraphobia. I ended up with psychotic depression, due to extreme untreated anxiety. I refused all meds. Finally, when I was coming out of it, I was able to get to a wonderful psychiatrist. She wasn't afraid of long term daily benzos. The ssris aren't kind to me either. I did give a small dose of Zoloft and remeron a good run for 2 yrs, but gained 30+lbs. My pdoc always let me take klonopin along with the antidepressants, and we determined that it was the one that I most needed. I tapered off the z and r, and am doing fabulous on .5mg klonopin. I take it at night, no side effects, no tolerance, and I don't raise the dose. I drink no alcohol, and I exercise and eat properly. So, with my anxiety under control, I have no depression, or panic, or psychosis. Good luck to u!

Does anyone here have any experience of being in a situation like this (i.e., where you can't take antidepressants), and/or does anyone have any experience of long-term benzo use?

I don't have direct experience, however, I can't tolerate SSRIs, the SNRIs I've tried aren't powerful enough and while I do great on very high dose TCAs they are likely to become problematic in older age because of their affect on the heart and CBT, while helpful, hasn't been the answer either, so I'm planning to see out my days hopefully medicated with benzodiazepines (BZDs) if I can find a doctor willing to prescribe them.

Unfortunately, that is the big problem with using BZDs, the uncertainty of being able to get them prescribed in the future, and the possibility of being forced to wean off them quickly if your doctors decide they want you off them.

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Just how likely is tolerance? From what I've read in the scientific literature, some people become tolerant quickly, while others never seem to develop it.

Yes, most people don't develop tolerance to benzodiazepines and generally need to take less over time. However, some do and there is no way of predicting how you will react, unfortunately. But the risk is small. According to a study I found quoted on probably the most anti of anti BZD websites:

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"The typical pattern of a drug dependence syndrome, with drug seeking behaviour, rapid tolerance, and escalation of dosage, is rare (according to Marks's calculations, one in every 5 million patient months "at risk")"Benzodiazepines on trial

If the quoted research is correct, and it sounds about right, then if all 314 million Americans took BZDs for 10 years, about 7,500 would develop tolerance; OTOH about 320,000 will die in auto accidents.

Given that you're probably need to take them daily, the longer acting BZDs - clonazepam (Klonopin), clorazepate (Tranxene), or diazepam (Valium) would be your best be. At least in epilepsy, tolerance develops less frequently with clorazepate than in the other two. Diazepam has a low potency so you need to take much higher doses of it than of clonazepam and clorazepate.

HOWEVER, all the above said, I think you should consider trying one of the TCAs. I know you've been on one, but unlike the SSRIs and SNRIs, there is a great variation in how they work. Some are as serotonergic as the SSRIs, others don't affect serotonin much at all. The two I think you should consider are nortriptyline (Aventyl, Pamelor) and doxepin (Silenor, Sinequan), in that order as doxepin is highly sedating. They are strong norepinephrine reuptake inhibitors with little affect on serotonin pathways.

Both are available in very small dose tablets (10mg nortriptyline, 6mg doxepin) compared to the minimum therapeutic dose (usually 75mg/day) which make it much easier to begin at a low dose that is unlikely to trigger much in the way of side-effects. If you keep increasing the dose by the same small amount every week you shouldn't have too many problems getting to the target dose.

NOTE: I'm not a doctor, and particularly not yours, so there may be factors I'm unaware of. Therefore all advice is of a general nature and you should consult your doctor before following any of it, especially before changing med doses.

U and I are similar. Except mine didn't go into agoraphobia. I ended up with psychotic depression, due to extreme untreated anxiety. I refused all meds. Finally, when I was coming out of it, I was able to get to a wonderful psychiatrist. She wasn't afraid of long term daily benzos. The ssris aren't kind to me either. I did give a small dose of Zoloft and remeron a good run for 2 yrs, but gained 30+lbs. My pdoc always let me take klonopin along with the antidepressants, and we determined that it was the one that I most needed. I tapered off the z and r, and am doing fabulous on .5mg klonopin. I take it at night, no side effects, no tolerance, and I don't raise the dose. I drink no alcohol, and I exercise and eat properly. So, with my anxiety under control, I have no depression, or panic, or psychosis. Good luck to u!

Thanks, hikingchik63. Do you mind if I ask how long you have been taking the clonazepam for? I assume you take it every night?

HOWEVER, all the above said, I think you should consider trying one of the TCAs. I know you've been on one, but unlike the SSRIs and SNRIs, there is a great variation in how they work. Some are as serotonergic as the SSRIs, others don't affect serotonin much at all. The two I think you should consider are nortriptyline (Aventyl, Pamelor) and doxepin (Silenor, Sinequan), in that order as doxepin is highly sedating. They are strong norepinephrine reuptake inhibitors with little affect on serotonin pathways.

I have tried 3 TCAs: amitriptyline, dothiepin, and trimipramine. I couldn't tolerate any of them, though for different reasons. Dothiepin seemed to work at first (I suspect because of the sedating effects), but as soon as that wore off, my anxiety got worse. So my psychiatrist suggested I increase the dose. Rinse and repeat. I got up to about 125 mg I think, before it was just intolerable.

I couldn't get beyond 45 mg of amitriptyline (although even at that dose I was heading towards hypomania), and the anticholinergic side effects were awful. I nearly had to be catheterised in hospital for urinary retention. Not fun.

All three of them affected my heart and blood pressure, making me tachycardic all the time. Not good for someone with anxiety, and someone who already has heart problems. I appreciate your comments, but I'm never touching another TCA again (or any other antidepressant for that matter).

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Given that you're probably need to take them daily, the longer acting BZDs - clonazepam (Klonopin), clorazepate (Tranxene), or diazepam (Valium) would be your best be. At least in epilepsy, tolerance develops less frequently with clorazepate than in the other two. Diazepam has a low potency so you need to take much higher doses of it than of clonazepam and clorazepate.

Yes, I think benzos may be my only option, too. The only thing is, I suspect I'll need quite a bit. 10 mg of diazepam daily isn't enough, and even 15 mg on "special occasions" isn't much better. I'm thinking I need at least 20 mg per day perhaps up to 30 mg.

It's hard to know what to think about tolerance. I've been searching PubMed and I've read all of the latest research. It seems to suggest that the risks of benzos have been greatly overstated, but how to convince a doctor of that? My GP is pretty good, but what do I do when she retires, or if I have to move? (I really do need to move for my career, and probably overseas, which will complicate matters. Needless to say, completely impossible at the moment).

There just seem to be so many anti-benzo doctors out there, and Australia seems to be moving down the road to restricting benzos. Alprazolam has now been rescheduled so that it is in the same class as morphine, just because a few idiots have been abusing it. Now my GP can't prescribe it without Health Department approval, and you have to sign a patronising "treatment contract" in which you promise that you won't abuse it. (I have used only alprazolam prn to stop really bad panic attacks).

I guess I have this fear that if I go down the benzo road, there is the risk that I might be one of the unlucky ones that develop tolerance, or that I'll end up in a situation where I can no longer be prescribed them. (Probably worrying too much about the latter, but you never know. I gather things are pretty tough regarding benzo access in the UK now).

I would feel more confident if I could hear about some long-term benzo success stories.

I have been on klonopin for 5 1/2 yrs. I do take it every night, 9pm. Im now able to fly, go to the dentist, etc. I used to have panic attacks in any new situation. I started out with brand and due to the expense, I switched over successfully to Teva generic clonazepam. Here, the drs r more accepting of benzo use, esp if u have been on it and r not increasing the dose constantly. Since Klonopin is so strong, u can get away with a smaller dose than valium. I have read this article over and over to educate myself about anxiety, and I thought u might want to look at it:[http://www.panic411.com//b]

I have tried 3 TCAs: amitriptyline, dothiepin, and trimipramine. I couldn't tolerate any of them,

Which is why I suggested nortriptyline and maybe doxepin. They are much, much less active on serotonin and acetylcholine muscarinic which I believe are responsible for your problems with antidepressants.

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Yes, I think benzos may be my only option, too. The only thing is, I suspect I'll need quite a bit. 10 mg of diazepam daily isn't enough, and even 15 mg on "special occasions" isn't much better. I'm thinking I need at least 20 mg per day perhaps up to 30 mg.

Most take 1-3mg Klonopin for good panic control, which is the equivalent of about 20-60mg of diazepam. Which may seem a lot, but to put it into perspective most Klonopin treated epileptics are on 10mg/day and 20mg isn't unheard of, which is 200-400mg of diazepam (and is why the high potency Klonopin was developed because taking that much Valium daily is difficult).

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I guess I have this fear that if I go down the benzo road, there is the risk that I might be one of the unlucky ones that develop tolerance, or that I'll end up in a situation where I can no longer be prescribed them. (Probably worrying too much about the latter, but you never know. I gather things are pretty tough regarding benzo access in the UK now).

Certainly, tolerance is a possibility, but I believe the uncertainty of getting them prescribed in the future is a much bigger one. Not only could you find it difficult finding a doctor willing to prescribe them if your current one fell under the proverbial bus or turned benzophobe, but anti benzo zealotry can see doctors insisting patients wean off within a couple of weeks which is criminal, IMHO. And the whole dependency issue is built on irrationality. Some of the antidepressants can be every bit as hard to discontinue.

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I gather things are pretty tough regarding benzo access in the UK now

It has been for a long time. You'd have a much better chance of winning the lottery than getting benzodiazepines through the NHS. The tide there is turning against antidepressants too with a concerted effort underway to get everyone into CBT, though the GFC has slowed this down in recent years as it is much more expensive.

NOTE: I'm not a doctor, and particularly not yours, so there may be factors I'm unaware of. Therefore all advice is of a general nature and you should consult your doctor before following any of it, especially before changing med doses.

I appreciate your comments, insights, but I don't think either nortriptyline or doxepin are a good idea. Nortriptyline is the main active metabolite of amitriptyline, so I don't think it's for me. I imagine it will be much like amitriptyline but with less anticholinergic activity. It's also more activating than amitriptyline, which is not a good idea for me. I found amitriptyline to be activating even at a low dose.

I'm also doubtful that doxepin will be any better than dothiepin/dosulepin. If anything, I need my noradrenaline levels lowered/blocked. Drugs like venlafaxine were a nightmare for me.

No, I am resolved never to take another antidepressant again. They just don't agree with me.

I guess I'll just have to see what my psychiatrist has to say.

On the subject of people developing dependence on antidepressants, you might find this paper interesting (if you haven't already seen it):

Nielsen M, Hansen EH, G°tzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction. 2012;107(5):900-8.

From the abstract:

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Withdrawal reactions to selective serotonin re-uptake inhibitors appear to be similar to those for benzodiazepines; referring to these reactions as part of a dependence syndrome in the case of benzodiazepines, but not selective serotonin re-uptake inhibitors, does not seem rational.

Nortriptyline is the main active metabolite of amitriptyline, so I don't think it's for me. I imagine it will be much like amitriptyline but with less anticholinergic activity.

No, it is not like amitriptyline which is as serotonergic as some SSRIs with a serotonin transporter binding potency of 20 Ki, whereas nortriptyline is one of the least with a potency of 100 Ki (the lower the Ki the greater the potency). However, you're correct about the anticholinergic activity, it's a far less.

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It's also more activating than amitriptyline, which is not a good idea for me. I found amitriptyline to be activating even at a low dose.

It is marginally less sedating than amitriptyline, but most, though not all, find it sedating.

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If anything, I need my noradrenaline levels lowered/blocked. Drugs like venlafaxine were a nightmare for me.

Unless you were taking 150mg plus it would have had little if any effect on noradrenaline. Its noradrenaline transporter affinity is up to 6,300 Ki. It was just another SSRI. None of the antidepressants you've listed has an appreciable noradrenaline impact.

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No, I am resolved never to take another antidepressant again. They just don't agree with me.

Cool.

I guess I'll just have to see what my psychiatrist has to say.

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On the subject of people developing dependence on antidepressants, you might find this paper interesting (if you haven't already seen it):

Nielsen M, Hansen EH, G°tzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction. 2012;107(5):900-8.

They are right, it isn't rational. Indeed, the entirety of the debate about benzodiazepines for anxiety is irrational. Unlike the debate about their use for epilepsy which is almost all rational. Withdrawal is mostly a non issue despite the much higher doses taken by epileptics.

In a number of studies1 since 1992, Charles Medawar, a noted UK pharmaceutical safety researcher has repeatedly found that the number of "Yellow Card" reports of adverse withdrawal effects involving antidepressants, mostly Paxil (paroxetine) and Effexor (venlafaxine), exceed not only that for benzodiazepines, but all other meds combined in most years.

IanReferences:

[1]Medawar C"Social Audit on the safety of medicines."International Journal of Risk and Safety in Medicine, 1992, 1994. (there have been others since but I don't have a list. Unfortunately, the studies are not available on-line)

NOTE: I'm not a doctor, and particularly not yours, so there may be factors I'm unaware of. Therefore all advice is of a general nature and you should consult your doctor before following any of it, especially before changing med doses.